American Journal of Medical Genetics 41:313-318 (1991)
Mucolipidosis wpe IV: Clinical Manifestations and Natural History ~~~
David Chitayat, Catherine M. Meunier, Kathy A. Hodgkinson, Kenneth Silver, Michael Flanders, Ilse J. Anderson, John M. Little, David A.H. Whiteman, and Stirling Carpenter Department of Pediatrics, Division of Medical Genetics (D.C., C.M.M.,KA.H.), Division of Neurology (K.S.), and Division of Ophthalmology (MP., J.M.L.), The Montreal Childrens Hospital and Department of Neurology, Neurosurgery and Pathology (S.C.), The Montreal Neurological Institute; McGill University, Montreal, Quebec, Canada, and Department of Pediatrics (Z.A., D.A.H.W.),University of Connecticut School of Medicine, Farmington
The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV. KEY WORDS: Lysosomal storage, electron microscopy, skin biopsy, conjunctival biopsy, corneal cloudiness, developmental delay, Ashkenazi-Jewish, pigmentary retinopathy, autosoma1 recessive inheritance. INTRODUCTION Mucolipidosis IV (ML IV) is an autosomal recessive lysosomal storage disorder characterized clinically by severe psychomotor retardation and corneal clouding [Amir et al., 19871. Most patients described are of Ashkenazi-Jewish origin although the gene frequency in this population is unknown. Transmission electron microscopic (TEM) studies show membrane-bound storage deposits in most tissues, including amniocytes and chorionic villi [Ornoy et al., 19871.The enzyme deficiency is
Received for publication August 31, 1990; revision received March 5, 1991. Address reprint requests to Dr. D. Chitayat, Montreal Children’s Hospital, Division of Medical Genetics, 2300 “upper Street, Montreal, Quebec, H3H 1P3, Canada.
0 1991 Wiley-Liss, Inc.
still unknown, although ganglioside sialidase has been reported as a possible candidate [Bach et al., 19791. We present five patients with ML IV ranging in age from 20 months to 32 years; the latter may be the oldest ML IV individual reported to date. All patients have been followed since birth and help illustrate the natural history and variability of this disease (Table I).
CLINICAL REPORTS Family A The parents were of Ashkenazi-Polish origin, nonconsanguinous, with an unremarkable family history. At the birth of their first son, the mother was 18and the father 24 years old. In total they have had three affected and three normal children. Patient 1. This young man was referred to our clinic at age 32 (Fig. 1).As a child he presented with hypotonia and strabismus, although head circumference (OFC) was normal. He sat unsteadily at 8 months and crawled at 1year. In his second year he became spastic and head growth decreased. At 5 years he had rudimentary grasping abilities, was unable to walk or talk, and had spastic quadriparesis, brisk deep tendon reflexes (DTRs), ankle clonus, tight heel cords, and bilateral Babinski signs. Pneumoencephalography documented cerebral atrophy, more marked in the right frontal, left parietal, and left temporal lobes, although EEG was normal. He learned to sit alone a t 7 years and could pull to a standing position a t 8 years. At the age of 12 he was institutionalized. Puberty began a t 20 years without a recorded growth spurt. The cause of his problems was recognized at 24 years after his brother (patient 3) was diagnosed. At 32 years he could not walk or sit alone and had difficulty chewing and swallowing.His height was 140.5 cm (
Mucolipidosis wpe IV: Clinical Manifestations and Natural History ~~~
David Chitayat, Catherine M. Meunier, Kathy A. Hodgkinson, Kenneth Silver, Michael Flanders, Ilse J. Anderson, John M. Little, David A.H. Whiteman, and Stirling Carpenter Department of Pediatrics, Division of Medical Genetics (D.C., C.M.M.,KA.H.), Division of Neurology (K.S.), and Division of Ophthalmology (MP., J.M.L.), The Montreal Childrens Hospital and Department of Neurology, Neurosurgery and Pathology (S.C.), The Montreal Neurological Institute; McGill University, Montreal, Quebec, Canada, and Department of Pediatrics (Z.A., D.A.H.W.),University of Connecticut School of Medicine, Farmington
The clinical manifestations and psychomotor development of five patients with mucolipidosis IV (MLIV) from three Ashkenazi-Jewish families are reported. The presenting symptoms were hypotonia, developmental delay, corneal clouding, and puffy eyelids. Four of the patients had convergent strabismus and none progressed beyond a developmental age of 15 months. One patient died of aspiration at 17 years while the oldest patient entered puberty at 20 years, developed a coarse face at 30 years, and is now 32 years old. Histopathological studies in four patients showed storage changes characteristic of MLIV. KEY WORDS: Lysosomal storage, electron microscopy, skin biopsy, conjunctival biopsy, corneal cloudiness, developmental delay, Ashkenazi-Jewish, pigmentary retinopathy, autosoma1 recessive inheritance. INTRODUCTION Mucolipidosis IV (ML IV) is an autosomal recessive lysosomal storage disorder characterized clinically by severe psychomotor retardation and corneal clouding [Amir et al., 19871. Most patients described are of Ashkenazi-Jewish origin although the gene frequency in this population is unknown. Transmission electron microscopic (TEM) studies show membrane-bound storage deposits in most tissues, including amniocytes and chorionic villi [Ornoy et al., 19871.The enzyme deficiency is
Received for publication August 31, 1990; revision received March 5, 1991. Address reprint requests to Dr. D. Chitayat, Montreal Children’s Hospital, Division of Medical Genetics, 2300 “upper Street, Montreal, Quebec, H3H 1P3, Canada.
0 1991 Wiley-Liss, Inc.
still unknown, although ganglioside sialidase has been reported as a possible candidate [Bach et al., 19791. We present five patients with ML IV ranging in age from 20 months to 32 years; the latter may be the oldest ML IV individual reported to date. All patients have been followed since birth and help illustrate the natural history and variability of this disease (Table I).
CLINICAL REPORTS Family A The parents were of Ashkenazi-Polish origin, nonconsanguinous, with an unremarkable family history. At the birth of their first son, the mother was 18and the father 24 years old. In total they have had three affected and three normal children. Patient 1. This young man was referred to our clinic at age 32 (Fig. 1).As a child he presented with hypotonia and strabismus, although head circumference (OFC) was normal. He sat unsteadily at 8 months and crawled at 1year. In his second year he became spastic and head growth decreased. At 5 years he had rudimentary grasping abilities, was unable to walk or talk, and had spastic quadriparesis, brisk deep tendon reflexes (DTRs), ankle clonus, tight heel cords, and bilateral Babinski signs. Pneumoencephalography documented cerebral atrophy, more marked in the right frontal, left parietal, and left temporal lobes, although EEG was normal. He learned to sit alone a t 7 years and could pull to a standing position a t 8 years. At the age of 12 he was institutionalized. Puberty began a t 20 years without a recorded growth spurt. The cause of his problems was recognized at 24 years after his brother (patient 3) was diagnosed. At 32 years he could not walk or sit alone and had difficulty chewing and swallowing.His height was 140.5 cm (
