Self-Mutilation in Neurodegeneration with Brain Iron Accumulation.

Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.

What was known?

Mineral deposition in the basal ganglia causing features of basal ganglia involvement with or without cognitive and behavioral complications. self mutilation is uncommon and there is only one case report.

Introduction

Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia.[1] This is seen due to mutations in the genes involved in iron metabolism pathways, phospholipid metabolism and lysosomal function. The genes known to be involved are PLAN (phospholipaseA2 group-associated neurodegeneration), PANK2 (pantothenate kinase-associated degeneration), FAHN (fatty acid hydroxylase-associated neurodegeneration), C19orfl2 gene (mitochondrial protein of unknown function) and a large group of idiopathic with iron accumulation.[2] It may be sporadic or familial. Common features are mental retardation, optic atrophy, dystonia, opistotonus, rigidity, choreoathetosis, spasticity and seizures.[3] Only one case is reported with self-mutilation in the world literature to our knowledge.[4] Based on the age of onset they are grouped into: Late infantile – till the age of 6 years; postinfantile – 7 to 15 years; adult – 22 to 64 years. Course is variable from rapid death to a prolonged stable course. Diagnosis is based on clinical features, radiological as well as genetic features. According to Swaiman et al. (1991), the obligate criteria are (1) onset in the first two decades, (2) progressive deterioration of signs and symptoms, (3) evidence of extra pyramidal involvement. Corroborative criteria include (1) optic atrophy, (2) intellectual deterioration, (3) corticospinal tract involvement, (4) family history, (5) autosomal recessive inheritance and (5) seizures. Self-mutilation in children is reported with Lesch Nyhan Syndrome, Gilles De la Tourette, Cornelia Delange syndrome, Neuroacanthocytosis, and Hereditary Insensitivity to Pain. Here we report a case of neurodegeneration with brain iron accumulation of late infantile type with severe self-mutilation of lips and episodic ophisthotonic posturing of the trunk with extension to both lower limbs precipitated by any attempted action.[1456]

Case Report

A 10-year-old girl born out of second degree consanguineous marriage presented with complaints of regression of both motor and mental milestones from the age of 4 years. She was born naturally at full term followed by mild delay in milestones; however, she was fully ambulant and communicating in sentences by the age of 3. Then it was noticed that she developed difficulty in walking in the form of abnormal posturing of the trunk which aggravated during attempted motor tasks of the limbs and exertion. Later she developed plantar flexed posture at both ankles, dystonic posturing and choreiform movements of both upper limbs followed by self-mutilating behavior in the form of biting at the base of her thumb, biting the lips and the tongue. Later she developed difficulty in chewing, swallowing and became bed bound. She could comprehend simple commands and was communicating through sounds and gestures which her mother could comprehend.

Examination showed an emaciated patient. Her head circumference was 42 cm, weight 11 kg and height 102 cm. She was able to understand simple commands. Examination of her lips showed ulcerated, swollen lower and upper lips [Figure 1]. Several parts of the lower lips were missing. The ulcers were showing yellowish slough with areas of bleed. Her angle of the mouth showed ulceration and pigmentation. Minor ulcerations were also seen over the tongue and two of her incisors were missing in the lower jaw. She was in ophisthotonic posture and the right thigh had crossed over to the left thigh with the right leg placed below the left knee [Figure 2]. Any attempt to move the right leg produced severe pain. Examination of her nervous system showed pallor of both optic discs. She had orofacial dystonia and apraxia for swallowing. There was retrocollis, opisthotonus of the trunk [Figure 3] with partial flexion at elbow, wrist, hip and knee. Choreiform movements were seen in both upper limbs. Her reflexes were well elicited and plantars were extensor.

Figure 1

(a) Ulcerated lips with loss of tissue. (b) Ophisthotonic posture and the right thigh was crossed over to the left thigh with the right leg placed below the left knee. (c) Retrocollis, opisthotonus of the trunk with partial flexion at elbow, wrist, hip and knee

Figure 2

Hip X-ray showing posterior dislocation of the right hip

Figure 3

(a-c) Magnetic resonance imaging of brain showing isointensity of the basal ganglia structures in T1-weighted images, hypointensity in the anteromedial putamen in T2-weighted images and FLAIR. SW sequences showed hypointensity in the putamen suggestive of iron deposition

She was investigated with blood tests and imaging. Her liver enzymes were elevated: Alanine transaminase was 173 U/l and aspartate transaminase was 534 U/l (normal value 8–50 U/L). Lactate dehydrogenase levels were elevated at 1208 U/l (normal < 248 U/l). Serum ceruloplasmin levels were 37 mg/dl (normal 20-35 mg/dl). Her peripheral smear showed normocytic to microcytic hypochromic blood picture. Her ferritin levels were in the lower limit of normal. There was no KF ring. Serum uric acid, serum copper and 24 hour urinary copper were normal. Urine screening for abnormal metabolites and tandem mass spectroscopy for inborn errors of metabolism was non-contributory. Her hip X-ray showed posterior dislocation of right hip [Figure 2]. Abdominal ultrasound showed coarseecho texture of liver suggestive of chronic liver disease. Cardiac evaluation was normal. Magnetic resonance imaging of Brain showed isointensity of the basal ganglia structures in T1-weighted images, hypointensity in the anteromedial putamen in T2-weighted images, and fluid attenuated inversion recovery (FLAIR) sequence. Susceptibility Weighted (SW) sequences showed hypointensity in the putamen suggestive of iron deposition[78] [Figures 3a-c] Quantification of iron could not be done due to technical reasons. Genetic testing could not be carried out because of financial constraints.

The patient was treated as follows: Ulcerations in the lips healed with local applications and antibiotics. Her general condition improved with Ryle's tube feeding. Endoscopic gastrostomy was planned but parents were not willing for the same. Considerable improvement in dystonia occurred with oral trihexyphenidate and baclofen. Orthopedic consultation was done and suggested surgery after good control of dystonia.

Discussion

This 10-year-old child presented with progressive generalized dystonia with opisthotonus, oromandibular dyskinesias, apraxia for swallowing and self-mutilating behavior. Well-known causes of self-mutilating disorders were excluded with appropriate investigations. She satisfied Swaiman et al's. criteria for NBIA. The mandatory criteria are onset during first two decades, choreoathetosis and dystonia, progressive course. All the three parameters were present. Corroborative criteria are corticospinal tract involvement evidenced by spasticity, progressive intellectual impairment, optic atrophy, seizures, and MRI evidence of hypo intensity in T2-weighted images in the basal ganglia. All these were present. The corroborative features which were absent are retinitis pigmentosa, family history and abnormal cytosomes in circulating lymphocytes and Sea Blue histiocytes in the bone marrow as they were not done since the criteria for diagnosis were already met. Other conditions were excluded as follows: Hereditary insensitivity to pain otherwise called human pin cushions are symptomatic from birth not appreciating any pain resulting in severe mutilation of lips, tongue, auto amputation of limbs and death within the first 5 years. Gilles de la Tourette manifests as multiple motor and vocal tics, coprolalia, and no other evidence of regression. Neuroacanthocytosis presents with progressive peripheral neuropathy, ataxia, retinitis pigmentosa, oromandibular dyskinesias and acanthocytes in the peripheral smear. Cornelia de Lange syndrome manifests as intrauterine growth retardation, low birth weight, mental retardation, microcephaly, facial dysmorphism in the form of arched eye brows which meet in the middle, low set ears, small upturned nose and widely spaced teeth, cleft lip and palate, short stature, deafness and autistic features. Lesch–Nyhan syndrome is an X-linked disorder, affects males which presents with athetosis, dystonia, chorea, and elevated uric acid with gouty arthritis. The above phenotypic characters clearly differentiate NBIA from these conditions. No case of self-mutilation in this condition is so far reported from India. MRI images were suggestive of brain iron accumulation. Her phenotypic characters were consistent with PANK2 mutation.[7] However, genetic testing and quantification of iron could not be done.

Conclusion

We report a case of recessively inherited very early onset ophisthotonic dystonia with retrocollis, oromandibular dyskinesia and severe self-mutilation. MR imaging showed brain iron accumulation suggestive of neurodegeneration with brain iron accumulation. This case is being reported as self-mutilation, a very rare complication with the above-mentioned conditions.

What is new?

Self mutilation is uncommon and there is only one case report in literature with this regard.