PMC4349522_01
Electron micrographs of brain from a frontal lobe biopsy in III-9 at age 5 years demonstrated abnormal appearing mitochondria and fibrillary astrocytic processes.
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F4
Electron micrographic studies of frontal cortex showed membrane-bound fibrillar reticular inclusions in several neurons, astrocytes and presumed mesenchymal cells associated with blood vessels and disorganized mitochondria (Fig. 4).
PMC4349522_02
Photos of affected males. (a) Individual III-10 at age 6 months, and (b) at age 5 years. (c) Individual IV-3 at 6 months and (d) vegetative, at age 14 years.
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F5
Figure 5 shows patient III-10 as an infant, 3a and several years later, 3b.
Histological sections from kidney, liver, and spleen from autopsy (III-9). a: Brown pigments in renal tubules (H&Ex100). b: The pigments were positive for iron-Prussian blue stain (x100). c: Cirrhotic nodules with fatty change (H&E, x200). d: Marked accumulation of hemosiderin in hepatocytes was present (Iron-Prussian blue stain, x 200). e: No grossly evident pigment deposition in spleen (H&E, x 100). f: Patchy iron deposition in spleen (Iron-Prussian blue stain, x 100).
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F6
Figure 5 shows patient III-10 as an infant, 3a and several years later, 3b. He had obvious ascites with marked splenomegaly and macro and micronodular cirrhosis, with extensive iron deposition in liver, kidney, pancreas, and gastrointestinal epithelium adrenal glands (Fig. 6).
Scant iron deposition in brain from autopsy (III-9):Basal Ganglia. a: Rare sections of basal ganglia showed brown pigments in neurons (H&E x 400). b: Iron-Prussian blue stain demonstrated that the pigments were positive for iron staining (x400).
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F7
Figure 5 shows patient III-10 as an infant, 3a and several years later, 3b. The deposition of iron in the basal ganglia was considered scant, and would not be uncommon in an older person, but considered possibly significant in light of the age of the subject (Fig. 7).
Evolution of skin lesions with age, individual IV-3. a: Ichthyosis, age 51/2 years. b: Yellowish brown plaque-like neck lesions, age 14 years. c: Streaky axillary and trunk hyperpigmentation, age 51/2 years. d: Elbow lesions, age 14 years.
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F8
In addition to their neurologic manifestations, the patients had ichthyosis or seborrheic dermatitis to varying degrees, with dryness and desquamation of plaque-like brownish scales most pronounced in the axillae and extending to the upper back, neck, and ears in a streak-like manner (Fig. 8).
Cutaneous and oral abnormalities, individual IV-3. (a) Epidermal microabscesses (b) microdontia, with widely spaced pointed teeth and gingival overgrowth are representative of those in all three affected males. c: Foot deformity and skin lesions, age 14 years.
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F9
Other cutaneous features included epidermal microabscesses involving the trunk and scalp, and circular lesions on palms and soles (Fig. 9a and c). Oral abnormalities included microdontia, widely spaced, and pointed teeth, and gingival overgrowth (Fig. 9b).
Neuroimaging features. Serial MRI images in individual IV-3 demonstrated progressive cerebellar and to a lesser extent cerebral atrophy and white matter loss at ages (a) 8 months, (b) 31/2 years, and (c) 51/2 years. d: Stir images performed at age 51/2 years failed to demonstrate excess brain iron deposition.
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F10
Figure 10 shows this progression for individual IV-3 with serial MRI imaging.
PMC4349522_03
Evolution of skin lesions with age, individual IV-3. a: Ichthyosis, age 51/2 years. b: Yellowish brown plaque-like neck lesions, age 14 years. c: Streaky axillary and trunk hyperpigmentation, age 51/2 years. d: Elbow lesions, age 14 years.
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F8
In addition to their neurologic manifestations, the patients had ichthyosis or seborrheic dermatitis to varying degrees, with dryness and desquamation of plaque-like brownish scales most pronounced in the axillae and extending to the upper back, neck, and ears in a streak-like manner (Fig. 8).
Cutaneous and oral abnormalities, individual IV-3. (a) Epidermal microabscesses (b) microdontia, with widely spaced pointed teeth and gingival overgrowth are representative of those in all three affected males. c: Foot deformity and skin lesions, age 14 years.
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F9
Other cutaneous features included epidermal microabscesses involving the trunk and scalp, and circular lesions on palms and soles (Fig. 9a and c). Oral abnormalities included microdontia, widely spaced, and pointed teeth, and gingival overgrowth (Fig. 9b).
Neuroimaging features. Serial MRI images in individual IV-3 demonstrated progressive cerebellar and to a lesser extent cerebral atrophy and white matter loss at ages (a) 8 months, (b) 31/2 years, and (c) 51/2 years. d: Stir images performed at age 51/2 years failed to demonstrate excess brain iron deposition.
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F10
Figure 10 shows this progression for individual IV-3 with serial MRI imaging.