New Pattern of Brain MRI Lesions in Isolated Complex I Deficiency

Abstract

We describe a boy presenting at the end of the first year of life with severely delayed motor development and only mild mental retardation. Neurological examination revealed axial hypotonia, mild ataxia and pyramidal signs. Elevated lactate and protein in cerebrospinal fluid were the most prominent laboratory abnormalities. Brain MRI showed severe supratentorial white matter changes. Cerebellar white matter appeared normal whereas the signal of the atrophic cerebellar cortex was markedly increased. In vivo ¹H-magnetic resonance spectroscopy of the parietooccipital white matter region showed a distinct resonance of lactate. By means of biochemical analysis of respiratory chain enzymes in fibroblasts, the diagnosis of an isolated complex I deficiency could be established in our patient.

Respiratory chain - white matter - cerebellum

References

• 1 Aicardi J, Castelein P. Infantile neuroaxonal dystrophy.  Brain. 1979;  102 727-748
• 2 Bentlage H A, Wendel U, Schagger H, ter Laak H, Janssen A, Trijbels F. Lethal infantile mitochondrial disease with isolated complex I deficiency in fibroblasts but with combined complex I and IV deficiencies in muscle.  Neurology. 1996;  47 243-248
• 3 De Lonlay-Debeney P, von Kleist-Retzow J C, Hertz-Pannier L, Peudenier S, Cormier-Daire V, Berguin P. et al . Cerebral white matter disease in children may be caused by mitochondrial respiratory chain deficiency.  J Pediatr. 2000;  136 209-214
• 4 Farina L, Nardocci N, Bruzzone M G, D'Incerti L, Zorzi G, Verga L. et al . Infantile neuroaxonal dystrophy: neuroradiological studies in 11 patients.  Neuroradiology. 1999;  41 376-380
• 5 Kim I O, Kim J H, Kim W S, Hwang Y S, Yeon K M, Han M C. Mitochondrial myopathy-encephalopathy-lactic acidosis-and stroke like episodes (MELAS) syndrome: CT and MRI findings in seven children.  Am J Roentgenol. 1996;  166 641-645
• 6 Loeffen J, Smeitink J, Trijbels F, Janssen A, Triepels R, Sengers R. et al . Isolated complex I deficiency in children: clinical, biochemical and genetic aspects.  Hum Mutat. 2000;  15 123-134
• 7 Mader I, Krägeloh-Mann I, Seeger U, Bornemann A, Nagele T, Kuker W. et al . Proton MR spectroscopy reveals lactate in infantile neuroaxonal dystrophy (INAD).  Neuropediatrics. 2001;  32 97-100
• 8 Munnich A, Rustin P. Clinical spectrum and diagnosis of mitochondrial disorders.  Am J Med Genet. 2001;  106 4-17
• 9 Rahman S, Blok R B, Dahl H HM, Danks D M, Kirby D M, Chow C W. et al . Leigh syndrome: Clinical features and biochemical and DNA abnormalities.  Ann Neurol. 1996;  39 343-351
• 10 Rahman S, Brown R M, Chong W K, Wilson C J, Brown G K. A SURF1 gene mutation presenting as isolated leukodystrophy.  Ann Neurol. 2001;  49 797-800
• 11 Rötig A, de Lonlay P, Chretien D, Foury F, Koenig M, Sidi D. et al . Aconitase and mitochondrial iron-sulphur protein deficiency in Friedreich ataxia.  Nat Genet. 1997;  17 215-217
• 12 Schuelke M, Smeitink J, Mariman E, Loeffen J, Plecko B, Trijbels F. et al . Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy.  Nat Genet. 1999;  21 260-261
• 13 Smeitink J, van den Heuvel L, DiMauro S. The genetics and pathology of oxidative phosphorylation.  Nat Rev Genetics. 2001;  2 342-352
• 14 Tanabe Y, Iai M, Ishii M, Tamai K, Maemoto T, Ooe K, Takashima S. The use of magnetic resonance imaging in diagnosing infantile neuroaxonal dystrophy.  Neurology. 1993;  43 110-113
• 15 Trijbels J M, Scholte H R, Ruitenbeek W, Sengers R C, Janssen A J, Busch H M. Problems with the biochemical diagnosis in mitochondrial (encephalo-)myopathies.  Eur J Pediatr. 1993;  152 178-184
• 16 Van der Knaap M S, Breiter S N, Naidu S, Hart A AM, Valk J. Defining and categorizing leukoencephalopathies of unknown origin: MR imaging approach.  Radiology. 1999;  213 121-133