Failure of siblings to thrive beyond 5 years of age.

We describe a family in which parents had consanguinity, being children of real sisters. They had given birth to five children. In their family, children remained healthy from birth to pre-school age and then started having symptoms around the age of 5 years and two of them succumbed to this illness. Polyglandular autoimmune syndrome Type-1 is a rare sporadic autosomal recessive disease. It is characterized by the existence of two or more endocrinal disorders. Patients may require lifelong hormone replacement therapy for survival.

INTRODUCTION

We describe a family in which parents had consanguinity being children of real sisters. They had given birth to five children. In their family, children remained healthy from birth to pre-school age and then started having symptoms around the age of 5 years and two of them succumbed to this illness.

Their first child, a male was asymptomatic until 5 years of age. He then started getting tonic clonic convulsions with uprolling of eyes and unresponsiveness lasting for few minutes, for which he was treated by neurologist for 3 years with antiepileptics including Dilantin. He was then referred to Department of Endocrines where we noticed hypotension and Bluish black pigmentation over lips, Chvostek and Trousseau sign were positive and curdy white deposits were noticed in the mouth. Other general and systemic examination was normal. He was investigated [Table 1] and Diagnosis was established and treatment was started. Patient could take treatment for just 2-3 days and then he had fever and vomiting and was hospitalized in a state of irritability and septicemic shock (total leukocytes counts - 55,900. He had tachycardia (heart rate - 160/min), hypotension (80/50 mm of Hg), tachypnea (RR - 38/min). He was given higher injectable antibiotics, ventilator support, inotropic support, but unfortunately, he couldn’t be revived and expired on 16-april-2011 at 12:50 AM. He was 8 years of age.

Table 1

Investigations of siblings and their parents

Their second child is a female 7 years of age, she had been asymptomatic until past 6 months, she then noticed weight loss, lethargy, weakness, increased craving for salty foods. She had a history of abnormal movements of hands and fingers since past 6 months and had hyperpigmentation of lips [Figure 1] since 4 months. Frequent Carpopedal spasms and white coated tongue [Figure 2] which was found to be due to moniliasis [Figure 3] was noted. She was brought to us, investigated [Table 1], diagnosed and put on treatment. She is in regular follow-up since last 6 months. There have been no abnormal movements, pigmentation of the lips and white deposits over tongue have regressed [Figure 4]. She is eating well and has gained weight.

Figure 1

Hyperpigmentation of lips

Figure 2

White coating over tongue

Figure 3

White deposits vanished after treatment

Figure 4

Moniliasis in microscope

Their third child a female had being healthy until 5 years of age and then died after a very brief illness. In retrospect, the parents recall that she had also had hyperpigmentation of the lips for 3 months and abnormal movements of hands and white curd like coated tongue for 3 months before death.

Their fourth child, a daughter, 3 years of age is healthy until date. Fifth child, a daughter of around 3 months is also healthy until date.

INVESTIGATIONS

Child 1 - Other Investigations

Bilirubin - 2.5 mg/dl, serum glutamic oxaloacetic transaminase - 109 IU/L, serum glutamic-pyruvic transaminase - 40.1 IU/L

Urea - 133.8 mg/dl, Serum creatinine - 1.43 mg/dl

Hb% - 9.2 g/dl, mean corpuscular volume - 89.3 fl, platelets - 49,000, C-reactive protein - 1.2 mg/L

Contrast enhanced computed tomography head - Basal ganglia calcification seen.

Child 2 - Index case

Thyroid profile - normal

Hb% - 11.6 gram%

MCV - 73.2 fl

Scraping of the tongue on potassium hydroxide mount showed fungal filaments [Figure 3]

Blood sugar levels were normal

Spleen normal, ear examination normal and no evidence of Otosclerosis

Fundus was normal.

DISCUSSION

Polyglandular autoimmune syndrome Type-1 (PGA 1)[1] is a rare autosomal recessive disorder, also known as Type I autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy or Whitaker syndrome is also referred as HAM (Hypoparathyroidism, Addison's disease, and Monaliasis) syndrome. A single gene mutation of autoimmune regulator,[2] which codes for a transcription factor featuring two zinc motifs, is believed to be likely pathogenic for PGA-I. PGA[3]-I has found increased correlation with human leukocyte antigen (HLA)-A28 and HLA-A3. People with PGA-1 have at least two of the disease's main symptoms: Fungal infections of the skin and mucous membranes, decreased function in the parathyroid glands and decreased function in the adrenal glands (primary adrenal insufficiency). Many people with the disease have all three main symptoms. Our index case of PGA 1[4] also presented with oral moniliasis, Features of hypoparathyroidism in the form of muscle spasm, tetany, weakness, with features of hypoadrenalism as salt craving, lethargy (hypoandrogen-metabolic syndrome). On treatment case improved and is living a fruitful life.

From this experience, we have learnt that, 1) In diagnosing PGA-1 history of consanguity is important. 2) In young patients presenting with convulsions, hypocalcemia should be kept as differential (hypoparathyroidism). 3) In patients of seizures, CT finding of Basal Ganglion calcification should alert us to look for Hypoparathyroidism. 4) In hypocalcaemic seizures using Dilantin/phenobarbitone may actually worsen the seizures because they have Antivitamin D effect.