Gm1 gangliosidosis associated with neonatal-onset of diffuse ecchymoses and mongolian spots.

A 7-month old girl with GM1 gangliosidosis type 1 manifested with diffuse ecchymosis and Mongolian spots. The cutaneous lesions were present at birth before the appearance of the other features of the disease. We postulate that dermal pigmentation may be recognized as an early sign of GM1 gangliosidosis.

Introduction

GM1 gangliosidosis is an autosomal recessive lysosomal storage disease caused by deficiency of the lysosomal hydrolase, acid beta-galactosidase. The infantile form (type 1) is characterized by progressive organomegaly, dysostosis multiplex, facial coarsening, and progressive neurologic deterioration within the first year of life. A variety of cutaneous signs have been described in children with GM1 gangliosidosis. We describe an infant with GM1 gangliosidosis associated with diffuse ecchymosis and Mongolian spots on the trunk and extremities with ventral and dorsal distribution.

Case Report

A 7-month-old girl was born to consanguineous Palestinian parents (i.e., first cousins) at term by cesarean section delivery due to fetal distress. At age of 2 weeks, she developed clonic seizures of upper and lower limbs. She was put on valproic acid when she was 2 months old. She was unable to sit, roll over, crawl, laugh or smile on social contact. She also had marked growth delay: weight 4 kg (-4 SD) and occipitofrontal circumference 40 cm (-2.5 SD). Her examination revealed generalized hypotonia, gingival hypertrophy, coarse facial features, diffuse ecchymosis and numerous diffuse Mongolian spots on her trunk and extremities [Figures 1–3]. Ophthalmologic exam showed bilateral macular cherry red spots. Enzyme assay in leukocytes confirmed deficiency of acid beta-galactosidase.

Figure 1

Numerous, diffuse ecchymoses and Mongolian spots on ventral surface of the trunk

Figure 3

Coarse facial features

Numerous, diffuse ecchymoses and Mongolian spots on dorsal surface of the trunk

The hyperpigmented skin lesions were apparent at birth and had not changed in number, position or size. A skin biopsy revealed dermal dendritic melanocytes (consistent with Mongolian spots) and also perivascular accumulation of foamy histiocytes (usually associated with storage disease).

The patient lacked any history of bleeding tendency and her platelet count, prothrombin time, partial thromboplastin time, bleeding time and fibrinogen level were all normal. Her electroencephalogram revealed irregular slow activity with occasional bursts and spikes of slow waves in a depressed background.

Discussion

Clinical and biochemical evidence supported the diagnosis of GM1 gangliosidosis type 1 in our patient. She had numerous and diffusely distributed hyperpigmented lesions which is an unusual presentation for typical Mongolian spots. She also had diffuse ecchymosis without an obvious cause.

Dermatologic findings are not commonly described in GM1 gangliosidosis. Eczematoid facial rash, truncal macular rash, angiokeratomas and generalized telangiectasia, in patients with this illness, have been sporadically described in the literature.[1-4] However, diffuse, extensive and unusual Mongolian spots have been reported in increasing number of cases of GM1 gangliosidosis type 1 in recent years.[5-7] Table 1 summarizes the reported cutaneous findings in these patients. This association has also been described with other lysosomal storage diseases such as Hurler's and Hunter's syndromes.[1112]

Table 1

Cutaneous findings reported in children with GM1 gangliosidosis

Weissbluth et al. reported the first case of possible chance association between GM1 gangliosidosis type 1 and extensive Mongolian spots in a 5-month-old female.[5] Selsor et al. reported a 10-month-old male with GM1 gangliosidosis type 1 who also had hyperpigmented macules and patches which were most probably Mongolian spots.[6] Beattie et al. described a 5-month-old female with GM1 gangliosidosis who had unusual Mongolian blue spots on her dorsal and central trunk.[7] Tang et al. presented a 13-month old child with GM1 gangliosidosis who had multiple Mongolian spots and further demonstrated swelling of the endothelial cells of the dermal capillaries with narrowing of the vascular lumen. The authors postulated that this may lead to weakening and dilatation of the vascular walls resulting in angiokeratoma and telangiectasia in these patients.[8] Hanson et al. described two infants with extensive dermal melanocytosis in association with GM1 gangliosidosis type 1 in one and with Hurler's syndrome in the other. They hypothesized that the accumulating metabolites in these illnesses may contribute indirectly to the arrest of the transdermal migration of melanocytes within the dermis leading to the appearance of these cutaneous findings. This may occur through interference with neural growth factor and tyrosine kinase-type receptor interactions.[11] Ochiai et al. described seven Japanese boys with Hunter's syndrome and reported extensive Mongolian spots in all of them; the authors suggested that the extent and persistence of the hyperpigmentation could allow earlier diagnosis and possible intervention before irreversible nervous system impairment develops.[12]

Conclusions

Although a chance association of the dermal findings and GM1 gangliosidosis cannot be excluded, we think our patient adds to the increasingly recognized evidence that patients with this disorder may manifest abnormal dermal pigmentary lesions, which may be present at birth thus helping physicians make an earlier diagnosis. Whether the ecchymosis in our patient is incidental or part of the dermal endothelial vasculopathy associated with GM1 gangliosidosis and other lysosomal storage diseases needs to be investigated further. We are not aware of this association in the literature and its significance in the diagnosis is not yet clear.