Lipemia retinalis in a 27 day old neonate: A case report.

Familial combined hyperlipidemia, which presents as hypercholesterolemia or hypertriglyceridemia, is the commonest form of genetic hyperlipidemia and is associated with premature coronary artery disease. This is a rare case report of a 27 day-old neonate born out of a third-degree consanguineous marriage, with grade III lipemia retinalis secondary to familial-combined hyperlipidemia.

Lipemia retinalis is a rare manifestation of both primary as well as secondary hyperlipidemia.[1] It was first described by Heyl in 1880 and occurs more commonly in patients with familial hyperchylomicronemia.[23] However, it may also be one of the manifestations of familial combined hyperlipidemia, which has a prevalence of 1--2% in the general population.[4] The characteristic fundoscopic changes include retinal blood vessel discoloration, which ranges from salmon pink to creamish white, depending on the level of plasma triglycerides.[1] Fundus changes become evident when the triglyceride levels exceed 2,500 mg/dl.[3]

Case Report

A 27-day-old newborn male was admitted in pediatric ward with chief complains of bleeding from the umbilicus and left ear since 1 day. The bleeding was profuse and light pink in color. Child was born at term, to parents with third-degree consanguineous marriage and was exclusively breastfed since birth. There was family history of hyperlipidemia in the mother and immediate maternal siblings.

Preabdominal examination revealed grade III hepatomegaly and grade II splenomegaly.

Ophthalmological evaluation was performed and revealed normal anterior segments of both eyes. Fundus examination revealed pale optic discs with peripapillary atrophy, salmon pink retinal background, and tortuous dilated milky white retinal blood vessels bilaterally, suggestive of lipemia retinalis [Fig. 1].

Figure 1

Fundus Photographs, (a) Right eye, (b) Left eye. In the photographs, a pale optic disc with peripapillary atrophy is visualized along with milky white retinal blood vessels and salmon pink retinal background (Source: By author)

During sampling, his blood was found to be highly viscous and milky. Total serum cholesterol was 4,560 mg/dl (normal range 50--92 mg/dl), serum triglycerides were 10,350 mg/dl (normal range 30--105 mg/dl), serum LDL was 498 mg/dl (normal range 3--39 mg/dl), and serum HDL was 16 mg/dl (normal range 23--58 mg/dl). Serum Apo B was 171 mg/dl (normal range 55--140 mg/dl).[5] Liver, kidney, and thyroid function tests were normal. Hb was 7.6 g/dl.

As genetic testing was not available, the neonate was clinically diagnosed to have lipemia retinalis secondary to familial-combined hyperlipidemia. Other causes of secondary hyperlipidemias, such as obesity, diabetes, liver disease, kidney disease, and hypothyroidism were ruled out in the newborn as well as family members.

The neonate was then weaned on skimmed milk and started on lipid lowering agents. Antibiotics, IV fluids, and blood transfusions were also given. However, the newborn succumbed to sepsis and passed away.

Google Scholar and PubMed databases were reviewed to ascertain the number of cases of lipemia retinalis which have been reported in newborns and infants less than 16 weeks, till the year 2018. To the best of our knowledge only 20 cases have been reported so far [Table 1].

Table 1

Literature review of cases of Lipemia Retinalis reported in newborns and infants less than 16 weeks, till 2018

Name of Study	Authors	Journal	Age/Sex of infant	Cause of Lipemia Retinalis
Lipemia Retinalis in a 29-day-old infant with type 1 hyperlipoproteinaemia.	Hayasaka et al., 1985[6]	British Journal of Ophthalmology	29 days/Female	Hyperlipoproteinemia
Lipemia Retinalis of prematurity	Ikesugi et al., 1996[7]	Archives of Ophthalmology	28 days (Premature baby born at 31 weeks)/Male	Hyperlipemia secondary to lipoprotein lipase deficiency
Lipemia Retinalis in a premature infant with type I hyperlipoproteinaemia	Rotchford et al., 1997[8]	Eye	11 weeks (Premature baby born at 26 weeks)/Female	Familial chylomicronemia
Lipoprotein lipase deficiency	Shankar et al., 1997[9]	Journal of Postgraduate Medicine	12 weeks/Male	Hyperlipemia secondary to lipoprotein lipase deficiency
Familial combined hyperlipidemia in a North Indian kindred	Sriram et al., 2005[4]	Indian Journal of Pediatrics	16 weeks/Male	Familial combined hyperlipidemia
Lipemia retinalis in a 35-day-old infant with hyperlipoproteinemia: case report	Cypel et al., 2008[10]	Abo-Arquivos Brasileiros Oftalmologia	35 days/Female	Hyperlipoproteinemia
Pink-creamy whole blood in a 3-month-old infant with a homozygous deletion in the lipoprotein lipase gene	Avis et al., 2010[11]	Clinical Genetics	12 weeks/Female	Hyperlipemia secondary to lipoprotein lipase deficiency
Grade III Lipemia Retinalis in a newborn	Čermàkovà et al., 2010[12]	Acta Ophthalmologica	28 days/Female	Hyperlipemia secondary to lipoprotein lipase deficiency
Lipoprotein lipase deficiency in an infant	Nampoothiri et al., 2011[13]	Indian Pediatrics	38 days/Male	Familial chylomicronemia
Lipemia Retinalis: case report and review of the literature	Zahavi et al., 2013[3]	Journal of American Association for Pediatric Ophthalmology and Strabismus	12 weeks/Male	Hyperlipemia secondary to lipoprotein lipase deficiency
An Infant with Milky Blood: An Unusual but Treatable Case of Familial Hyperlipidemia	Chaurasiya et al., 2013[14]	Indian Journal of Clinical Biochemistry	8 weeks/Male	Familial hyperlipidemia
A 3-day-old neonate with severe hypertriglyceridemia from novel mutations of the GPIHBP1 gene	Buonuomo et al., 2015 [15]	Journal of clinical Lipidology	3 days/Female	Familial chylomicronemia with GPIHBP1 gene mutation
Lipemia Retinalis	Chaudhury et al., 2015[1]	Delhi Journal of Ophthalmology	12 weeks/Female	Hypertriglyceridemia
Familial Chylomicronemia Syndrome (FCS) in a 10- Day- Old Neonate: A Case Report	Manzoor et al., 2015[16]	International Journal of Pediatrics	10 days/Female	Familial chylomicronemia syndrome (FCS)
Severe Hypertriglyceridemia due to a novel p.Q240H mutation in the Lipoprotein Lipase gene	Soto et al., 2015[17]	Lipids in Health and Disease	11 weeks (Premature baby born at 26 weeks)/Male	Hypertriglyceridemia secondary to p.Q240H mutation in the lipoprotein lipase gene
Exceptionally elevated triglyceride in severe Lipemia Retinalis	Yin et al., 2016[18]	International Medical Case Reports Journal	6 weeks/Female	Hypertriglyceridemia
Extreme hypertriglyceridemia, pseudohyponatremia, and pseudoacidosisin a neonate with lipoprotein lipase deficiency due to segmental uniparentaldisomy	Ashraf et al., 2017[19]	Journal of clinical Lipidology	36 days/Female	Hyperlipemia secondary to lipoprotein lipase deficiency
Familial chylomicronemia: A rare case report	Sowjanya et al., 2017[20]	Indian Journal of Case report	5 days/Female	Familial chylomicronemia
Lipemia Retinalis in a 1 month old infant	Jain et al., 2017[21]	Oman Journal of Ophthalmology	28 days/Female	Hyperlipemia secondary to lipoprotein lipase deficiency
Lipemia Retinalis in an infant treated for retinopathy of prematurity	Jain et al., 2017[22]	Journal of American Association for Pediatric Ophthalmology and Strabismus	14 days (Premature baby born at 30 weeks)/Female	Hypertriglyceridemia

Discussion

Hyperlipidemias may be classified as primary or secondary. Primary hyperlipidemias are mainly genetic and include conditions listed in Table 2.[23] Secondary hyperlipidemias are attributed to lifestyle and other factors such as diabetes, liver or kidney disease, hypothyroidsm, alcohol abuse.

Table 2

Conditions causing Primary Hyperlipidemia

Genetic Hyperlipidemias
Disorder	Mechanism
Familial hypercholesterolemia	LDL receptor defect
Familial defective Apo B-100	Apo B (LDL receptor-binding region) defect
PCSK9 gain of function mutations	Increased degradation of LDL receptors
Polygenic hypercholesterolemia	Unknown; Multiple mechanisms
LPL deficiency	Endothelial LPL defect
Apo C-II deficiency	Apo C-II; Functional LPL deficiency
Familial hypertriglyceridemia	Unknown; Multiple mechanisms
Familial combined hyperlipidemia	Unknown; Multiple mechanisms
Familial dysbetalipoproteinemia	Apo E; Reduced chylomicron and VLDL clearance
Primary hypoalphalipoproteinemia	Unknown; Multiple mechanisms
Familial Apo AI deficiency/mutations	Apo AI
Familial LCAT deficiency	LCAT gene
Fisheye disease (partial LCAT deficiency)	LCAT gene
Tangier disease	ABCA1 gene
Familial HDL deficiency	ABCA1 gene
Hepatic lipase deficiency	Hepatic lipase
Cerebrotendinous xanthomatosis	Hepatic mitochondrial 27-hydroxylase defect
Sitosterolemia	ABCG5 and ABCG8 genes
Cholesteryl ester storage disease and Wolman disease	Lysosomal acid lipase deficiency

Source: Goldberg[

Lipemia retinalis is the ocular manifestation of marked hyperlipidemia, more commonly hypertriglyceridemia, and fundus changes begin to manifest when the serum triglyceride level exceeds 2,500 mg/dl.[3] It starts off by affecting the periphery and later the posterior pole of the retina.[24] The grading system of lipemia retinalis has been given by Vinger et al.[25] [Table 3]. The arteries as well as veins assume the creamish milky white color and can be distinguished only by their size. However, reversal of signs may be expected with the reduction of serum triglyceride levels.[26] According to the above grading system, the neonate in this case report was found to have grade III changes.

Table 3

Grading of Lipemia Retinalis

Grade	Intensity	Clinical Appearance
I	Early	White and creamy aspect of peripheral retinal vessels
II	Moderate	Creamy-colored vessels extending towards optic disc
III	Marked	Salmon-colored retina, all vessels having milky aspect

Source: Vinger and Sachs[

Familial combined hyperlipidemia, which shows prevalence of 1--2% in the general population, is the commonest form of genetic hyperlipidemia and carries a high risk of premature coronary artery disease. This condition should be ruled out in any child presenting with high levels of serum total cholesterol and serum triglycerides, with a positive family history of hyperlipidemia, as there is no single diagnostic marker for this condition.[427]

As per our literature review, very few cases of lipemia retinalis have been reported in newborns and infants. Out of the 20 cases which we reviewed, seven cases were reported in male infants, out of which only three were in newborn males. Out of these three cases, one was reported in a 38-day-old male and was found to be secondary to familial chylomicronemia and the other two were reported in premature babies, the former being in a 28-day-old neonate born at 31 weeks gestation, which was due to familial hyperlipidemia secondary to lipoprotien lipase deficieny, whereas the latter was in a 11-week-old infant born at 26 weeks gestation which was secondary to hypertriglyceridemia because of p.Q240H mutation in the lipoprotein lipase gene. Among female newborns, the youngest case has been reported in a 3-day-old neonate, which was secondary to familial chylomicronemia with GPIHBP1 gene mutation.

To the best of our knowledge, no other case of familial combined hyperlipidemia showing grade III lipemia retinalis, with such markedly elevated serum total cholesterol and serum triglycerides levels, has been reported in a neonate as young as 27 days, which makes this case report unique.

Furthermore, it was also noticed in the literature review that few cases of lipemia retinalis have been accidentally detected while screening premature newborns for retinopathy of prematurity. This warrants appropriate referral of suspicious cases and their detailed ophthalmological evaluation in order to detect the presence of lipemia retinalis.

Medical management in patients with familial-combined hyperlipidemia consists of restriction of dietary fats, such as the use of skimmed milk in this case and use of lipid lowering drugs such as statins, which have proven safety and efficacy for short-term use in newborns and infants.[28]

Conclusion

Persistent and uncontrolled hypercholesterolemia and hypertriglyceridemia, especially in newborns and infants, can lead to other morbidities such as premature atherosclerosis and coronary artery disease, pancreatitis, hepatic failure, which may be fatal.[27] Hence, early detection and demonstration of lipemia retinalis in such cases is important.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.